(1) Field of the Invention
The present invention relates to a process for the preparation of protected trialkylammonium salts, particularly in chiral form. The trimethylammonium salts are particularly useful in the preparation of L-carnitine, a key intermediate for pharmaceutical compounds. In particular, the present invention relates to a process for the preparation of (2,2-dimethyl-1,3-dioxolan-4-ylmethyl)trialkylammonium salts, particularly in chiral form.
(2) Description of Related Art
L-carnitine is a key intermediate for the preparation of many pharmaceutical compounds. 1,2-dihydroxypropyl trimethylammonium salts 6 (see Scheme 1) have been employed in two routes to L-carnitine. The use of this intermediate is not of industrial significance, however, because of the substantial cost of the key optically pure 3-carbon starting materials, epichlorohydrin and chloro-dihydroxy propane. In the first synthesis, (S)-epichlorohydrin is treated with trimethylamine to form (S)-1-chloro-2-hydroxypropyltrimethylammonium sulfate. This is then converted to a nitrile by displacement of the chloro group with cyanide. Hydrolysis yields L-carnitine 9 as shown in Scheme 3 (Reimschuessel et al, U.S. Pat. No. 4,594,452 (1986); Kimbrell and Russell, U.S. Pat. No. 5,077,435 (1991)). In the other synthesis route, treatment of (R)-1-chloro-2,3-dihydroxypropane with trimethylamine produces 1,2-dihydroxypropyl trimethylammonium salts which structure is shown by 6 in Scheme 1. The diol 6 is then converted to (S)-3-chloro-2-hydroxypropyl trimethylammonium chloride by treatment with thionyl chloride. This is then hydrolyzed to yield L-carnitine (Katayama et al., U.S. Pat. No. 4,814,506 (1989)). There is a need for an economical and reliable process.